Iomai corporation's objective in the HIVRAD program is to induce robust systemic and mucosal neutralizing antibody responses via our novel skin immunization technology using candidate SIVand HIV antigens revealed by the Reinherz investigations. Iomai is the leader in skin delivery technology and will apply our immunological and formulation expertise to develop a dry patch vaccine product for topical delivery of novel SIV and HIV antigens. We will accomplish our objective by a systematic approach at understanding antigen delivery and formulation issues relating to each antigen and applying the information towards a highly efficient methodology for skin immunization. We will measure the effectiveness of all variations in skin immunization techniques and in antigens by quantitating homologous and heterlogous virus neutralizing antibody responses (see Core C). First, topical antigen delivery techniques will be assessed by applying antigen to hydrated skin, or to skin pretreated with wetting agents or physical treatments. Second, enhanced delivery of the SIV and HIV antigens will be accomplished through targeting the proteins to surface receptors expressed on epidermal Langerhans cells through the production of fusion proteins or in different expression systems. Finally, the HIV antigens, optimized for skin immunization, will be formulated with adjuvant into a dry patch product and evaluated for in vitro and in vivo potency. If successful, highly immunogenic dry patch products will be selected for efficacy of skin delivery in a non-human primate virus challenge model.